Echocardiography in Pediatric and Adult Congenital Heart Disease, 2nd Ed.

27. Cardiac Tumors

The term cardiac tumor is often used when referring to cardiac neoplasms. It is important to note, however, that it actually may refer to any mass-forming lesion within the heart–either neoplastic or otherwise. Non-neoplastic masses include such entities as thrombus, cyst, fat, abscess, ectopic tissue, and scar. Cardiac neoplasms include lesions that arise primary to the heart (either benign or malignant) and those that arise in other locations and metastasize to the heart (malignant by definition). Before the advent of echocardiography, the true incidence of primary cardiac neoplasms in children was elusive. With echocardiography, the incidence per echocardiogram performed approximates 0.08%. In children, the vast majority of primary cardiac neoplasms are histologically benign; fewer than 10% are malignant. Secondary or metastatic neoplasms of the heart are relatively rare in children. In children, rhabdomyomas are the most common primary cardiac neoplasm, whereas in adults, myxomas and papillary fibroelastomas are the most common (Table 27.1Fig. 27.1). Echocardiography is the primary imaging modality to diagnose cardiac tumors, whereas magnetic resonance imaging (MRI) and computed tomography can be useful adjunctive imaging modalities. Although most cardiac tumors in children are histologically benign, if their location in the heart jeopardizes cardiac, valvular, or conduction system function, then they can be associated with serious hemodynamic compromise and death.

SYMPTOMS AND PHYSICAL FINDINGS

In general, the physical findings of cardiac tumors depend on the location and size of the mass. If the mass is causing restriction to flow through a valve, there may be a murmur suggestive of stenosis, or if the obstruction is severe, there may be evidence of reduced cardiac output and even shock. Obstruction of the tricuspid valve, especially in a neonate, can be associated with cyanosis. Mitral valve obstruction or pulmonary venous obstruction can cause pulmonary edema and features of pulmonary hypertension. If the mass is preventing normal closure of a valve, there may be a murmur of valvular insufficiency.

Myxomas and papillary fibroelastomas have the potential for embolism, either from themselves or surface thrombus, and physical findings associated with pulmonary or systemic embolic phenomenon can be apparent. Because these tumors can be sessile, sudden occlusion of a cardiac valve or a coronary artery can result in sudden death.

Pericardial teratomas may cause a pericardial effusion. Hence, the heart sounds may be muffled, and pulsus paradoxus can occur along with hepatomegaly. Teratomas can cause distortion of the heart, which can be associated with superior or inferior vena cava obstruction and the physical findings attendant to the obstruction.

FIGURE 27.1. Distribution of intracardiac masses removed from 75 adult patients at Mayo Clinic from 1993 through 1998. AV, aortic valve; IVC, inferior vena cava; LA, left atrium; LAA, left atrial appendage; LV, left ventricle; MV, mitral valve; RA, right atrium; RV, right ventricle; SVC, superior vena cava; TV, tricuspid valve. (From Oh JK, Seward JB, Tajik AJ. The Echo Manual, 3rd ed, Lippincott Williams & Wilkins. © 2006 Mayo Foundation for Medical Education and Research.)

RHABDOMYOMA

Rhabdomyomas are the most common primary cardiac neoplasm in infants and children, accounting for 50%–75% of these tumors. In fact, more than 90% of intracardiac tumors found prenatally are rhabdomyomas. They are characterized by well-circumscribed, nonencapsulated white or white-gray masses that consist of vacuolated cells (“spider cells”) filled with glycogen. They are classified as hamartomas and do not undergo mitotic division. They can be entirely intramural or extend into the atrial or ventricular cavities. Most frequently, they involve the ventricular walls and cavities. There are multiple rhabdomyomas in 90% of cases.

Most patients with rhabdomyomas are asymptomatic. However, sudden death has occurred with these tumors. Protrusion of the mass underneath the pulmonary or aortic valve can produce significant left or right ventricular outflow tract obstruction. As noted, arrhythmias can be associated with rhabdomyomas as well.

Rhabdomyomas are quite echogenic and usually are multiple, homogeneous, and well circumscribed. They frequently have a speckled pattern. Although they can occur anywhere in the heart, usually they are present within the ventricular walls and often have a variable amount of extension into the ventricular cavity (Fig. 27.2). Occasionally they can be pedunculated. In contrast to thrombi, myxomas, vascular tumors, or fibromas, rhabdomyomas do not have echolucent areas indicative of hemorrhage or areas of calcification. These tumors can cause either right or left ventricular outflow tract obstruction but characteristically do not embolize. Serial echocardiography often reveals decreasing rhabdomyoma size, and, if present, right or left ventricular outflow tract obstruction may decrease over time.

There is a strong association of rhabdomyomas with tuberous sclerosis complex, and approximately 80% of children with these tumors have features thereof. Tuberous sclerosis is an autosomal dominant condition caused by mutations in the genes TSC1 and TSC2, encoding for the regulatory proteins hamartin and tuberin, respectively. It is manifest clinically by subungual fibromas, café-au-lait pigmentation, and subcutaneous nodules. About half of patients with tuberous sclerosis will have cardiac rhabdomyomas, but upwards of 80% of fetuses with rhabdomyomas have tuberous sclerosis. This decrease in prevalence with age is likely because of the propensity of the lesions to undergo spontaneous regression.

Because rhabdomyomas frequently regress, if they are causing no hemodynamic compromise and there appears to be no potential for them to embolize, they should be observed. Operation is indicated to remove them only if they are causing hemodynamic compromise or there is high risk of embolization. Recently, pharmacologic inhibition of the mTOR pathway has shown promise in hastening the regression of these tumors without surgical intervention.

MYXOMA

Considering patients of all ages, cardiac myxomas are the most common cardiac tumor generally coming to medical attention in the third to sixth decades of life. In children, however, they are second in frequency to rhabdomyomas. Three-quarters of myxomas are located in the left atrium (Fig. 27.3), and 25% are in the right atrium (Fig. 27.4A) They can be readily demonstrated by echocardiography in the subcostal and apical views. They occur rarely in the ventricles (Fig. 27.4B). They are friable, pedunculated, red lobular tumors (Fig. 27.5). They are histologically characterized by the presence of bland spindled cells proliferating in a myxoid background that contains numerous small blood vessels. In the atrium, the stalk typically is attached to the atrial septum (Fig. 27.6). When they occur in multiples, it is usually in the context of the Carney complex (myxoma syndrome). They are not believed to undergo malignant transformation.

FIGURE 27.2. A: Large right ventricular rhabdomyoma demonstrated as a homogeneous echogenic mass along the anterior wall of the outflow tract. This infant had successful resection of the obstructive mass. Pulmonary valve (PV). B: Large rhabdomyomas in the left ventricle (LV) apex and outflow tract. The LV outflow mass was successfully resected (Video 27.1). C: Fetal echocardiograph in four-chamber projection demonstrating multiple rhabdomyomas in the septum and lateral wall of the left ventricle. One large rhabdomyoma causes compression of the left ventricular cavity (Video 27.2). (Courtesy of Drs. Alexander Sokolov and Galina Martzinkevich, Tomsk Cardiac Center, Tomsk, Russia.)

In infants, a myxoma can mimic a variety of congenital heart defects. In children, they frequently cause relative obstruction of the tricuspid or mitral valve. Doppler echocardiography is very helpful to evaluate the hemodynamic impact of these tumors on atrioventricular valve inflow. Large myxomas can entirely obstruct the valve and be lethal. Partial obstruction of the mitral valve can cause pulmonary hypertension. The symptoms of valvular obstruction can be positional as the mass moves in and out of the valve orifice, with changing from standing to supine positions. The patient may experience positional dyspnea, dizziness, and/or syncope. Myxomas can be associated with the triad of (a) valvular obstruction, (b) embolic events, and (c) systemic illness. Constitutional symptoms, likely due to tumor elaboration of interleukin-6 (IL-6), include fever, malaise, weight loss, arthralgias, and myalgias. The patient also may exhibit anemia, thrombocytopenia, elevated sedimentation rate, and elevated gamma-globulin levels. The manifestations of a myxoma can be protean and be confused with rheumatic fever, endocarditis, septicemia, myocarditis, and collagen vascular diseases.

FIGURE 27.3. Large myxoma in the left atrium attached to the atrial septum. Movement with the cardiac cycle can be appreciated in these systolic (left) and diastolic (right) images. (From Oh JK, Seward JB, Tajik AJ. The Echo Manual, 3rd ed, Lippincott Williams & Wilkins. © 2006 Mayo Foundation for Medical Education and Research.)

FIGURE 27.4. Myxoma. A: Large myxoma in the right atrium. B: Parasternal short-axis view demonstrating a large myxoma in the right ventricular outflow tract (arrows). In young patients, a myxoma in an unusual location is probably related to familial myxoma syndrome. RA, right atrium; LA, left atrium. (From Oh JK, Seward JB, Tajik AJ. The Echo Manual, 3rd ed, Lippincott Williams & Wilkins. © 2006 Mayo Foundation for Medical Education and Research.)

The Carney complex is a familial form of myxoma that is manifest by the presence of a set of findings, including myxomas (cardiac or extracardiac), lentigines (Fig. 27.7), endocrinopathies, as well as a number of extracardiac neoplasms. If Carney complex is suspected, appropriate genetic screening should be undertaken in the patient and their family members, as well as surveillance for cardiac myxomas.

FIGURE 27.5. Pathologic specimen demonstrating a large myxoma (M) in the left atrium (LA).

The treatment of myxomas is surgical removal. Tumor recurrence is common in the setting of the Carney complex, but quite rare in the setting of an isolated tumor with complete excision.

FIBROMA

Cardiac fibromas are benign tumors that are likely hamartomatous in nature. They occur in infancy and rarely are identified in older children, adolescents, or adults. Grossly, fibromas are firm, white, nonencapsulated tumors most often in the left ventricular wall (free wall > septum), often at the apex (Figs. 27.8 and 27.9). If they protrude into the chamber, they can be broad-based or pedunculated. Despite the fact that these tumors often appear grossly well circumscribed, they do exhibit extensive microscopic interdigitation with the adjacent myocardium, making them difficult to completely resect. Despite this fact, the overall rate of recurrence following surgical excision is quite low.

FIGURE 27.6. Transesophageal four-chamber image demonstrating an atrial myxoma with attachment of the stalk to the region of the fossa ovalis.

FIGURE 27.7. Typical facies of a patient with Carney syndrome. Note the numerous lentigines. (Courtesy of Dr. James Seward.)

Fibromas can affect the right ventricle or the atria. These tumors may also compromise atrioventricular valve architecture and function, resulting in significant valvular regurgitation. Echocardiographically, fibromas appear as a single, bright, intramural echogenic mass that may invade the ventricular cavity resulting in impaired filling or significant outflow tract obstruction (Figs. 27.10 and 27.11). On imaging, they can be distinguished from rhabdomyomas because of their propensity to have multiple areas of calcification and cystic degeneration. Using strain imaging, fibromas are not compressed during the cardiac cycle. MRI may be useful in distinguishing them from rhabdomyomas. The clinical features and hemodynamic consequences of fibroma are similar to those of rhabdomyomas.

FIGURE 27.8. Pathologic specimen demonstrating a bright white fibroma at the left ventricular apex.

Cardiac fibromas may arise in the setting of the Gorlin syndrome (nevoid basal cell carcinoma syndrome), an autosomal dominant condition characterized by cardiac fibromas, multiple basal cell carcinomas, jaw cysts, and skeletal abnormalities. While cardiac tumors arise in fewer than 20% of those with Gorlin syndrome, the association is more than a mere coincidence and cardiac screening of those carrying a diagnosis of Gorlin syndrome is warranted.

FIGURE 27.9. A–D: Sequential intraoperative photographs during excision of a large fibroma from the left ventricular apex in a 3-year-old child. (Courtesy Dr. Joseph Dearani.)

FIGURE 27.10. Parasternal long-axis image of the large cardiac excised fibroma shown in Figure 27.9. Note the homogeneous echogenic appearance.

Due to the risk of sudden death from refractory ventricular arrhythmia, our center has favored surgical removal of large fibromas. If the fibroma is located within the atrioventricular groove and is intimate with a coronary artery, then surgical removal may be hazardous and these patients may be observed.

HETEROTOPIAS AND GERM CELL TUMORS

Displaced tissue during embryogenesis may lead to the formation of a number of tumors, most of which are, at least in part, cystic. These include benign cystic tumor of the atrioventricular (AV) node, bronchogenic cysts, and germ cell tumors (most commonly, teratoma).

Cystic tumor of the AV node is a congenital cystic mass located within the atrioventricular septum. It is most likely the result of ultimobranchial heterotopia and is histologically benign. Given its precarious location in or near the region of the atrioventricular node, it most commonly comes to attention at the time of autopsy following sudden death, though rare reports of antemortem diagnosis exist. Bronchogenic cysts are likewise a histologically benign cystic lesion that is most often intrapericardial and incidental.

FIGURE 27.11. Para-apical four-chamber image demonstrating the lateral and apical extent of the excised fibroma shown in Figure 27.9.

Intrapericardial teratomas usually are single encapsulated tumors containing multiple cysts within a mucoid stroma and are often located at the base of the heart. Rarely they can undergo malignant degeneration. Typically they are diagnosed in the neonate or newborn. They can also be diagnosed in utero in which case there is often coexistent hydrops and pericardial effusion. Intrapericardial teratomas can be associated with pericardial effusion and can compress cardiac structures such as the right atrium and ventricle. If they cause rotational displacement of the heart, superior vena cava obstruction can occur. Intracardiac teratomas are less frequent than intrapericardial teratomas and usually occur on the right side of the heart.

Infants with a teratoma typically present with respiratory distress, pericardial effusion, signs of cardiac compression, cardiac tamponade, and/or nonimmune hydrops fetalis. Echocardiographically, they are usually a single nonhomogeneous, lobular, intrapericardial mass and almost always are associated with pericardial effusion. Death can occur from rupture of cysts within the teratoma, causing cardiac tamponade. These tumors should be removed surgically.

HEMANGIOMA

Hemangiomas are benign neoplasms composed primarily of blood vessels. Cavernous, capillary and arteriovenous malformation types have been described. Most of these tumors are found incidentally, though symptoms may arise as a result of a pericardial effusion (bloody or nonbloody). The ventricular free walls are the most commonly described locations for hemangiomas to arise, though atrial tumors (both epicardial and endocardial) have been reported. Echocardiographically, these tumors are usually hyperechoic and have an intracavitary (or polypoid) pattern of growth. As predicted, these tumors often exhibit striking enhancement on magnetic resonance imaging, owing to their vascular composition.

PAPILLARY FIBROELASTOMA AND LAMBL EXCRESCENCES

In adults, papillary fibroelastoma is likely the most common primary cardiac neoplasm. They usually are single, small (less than 1.5 cm) and echocardiographically have a dense central core with a shimmering peripheral appearance (Fig. 27.12A). Grossly, these lesions are characterized by numerous fronds arising from a central stalk, causing them to be likened to sea anemones (Fig. 27.12B,C). They occur most frequently on the aortic (Fig. 27.13) and mitral valves, but may arise on any endocardial surface. Their propensity to arise on damaged endocardial surfaces (following instrumentation or in the setting of hypertrophic obstructive cardiomyopathy) has led most to believe they are likely a reactive phenomenon. Most patients are asymptomatic but papillary fibroelastomas can be associated with embolization (either from the tumor fronds themselves or surface thrombus) and resultant stroke, angina, and sudden death. Therefore, surgical excision is recommended.

FIGURE 27.12. A papillary fibroelastoma on the atrial surface of the anterior mitral leaflet. A: Parasternal long-axis image. Surgical excision is recommended due to the risk of embolization. B: Pathologic specimen of a papillary fibroelastoma that had been removed from the anterior leaflet of the mitral valve in an adult patient. C: Scanning electron micrograph of a papillary fibroelastoma with multiple fronds resembling a sea anemone.

Lambl excrescences (Fig. 27.14) are similar to papillary fibroelastomas, but less complex in architecture, usually manifesting as singular fronds arising exclusively on the closing surfaces of valves. Lambl excrescences are almost exclusively found on valves of older adults, but have been recently reported in children by our center.

FIGURE 27.13. A large papillary fibroelastoma on the aortic surface of the valve. A: Transesophageal echocardiographic image of the aortic valve in longitudinal projection. B: Pathologic specimen demonstrating a papillary fibroelastoma attached to an aortic valve cusp.

FIGURE 27.14. Pathologic specimen of an aortic valve with Lambl excrescences. These strands of fibrous tissue are typically present on the closing surface of the semilunar valve cusps and rarely are of any clinical significance. They should not be confused with thrombi or papillary fibroelastomas.

PHEOCHROMOCYTOMA

Primary cardiac pheochromocytomas (extra-adrenal paragangliomas) are very rare. These tumors have been reported primarily in women, and they have a unique and characteristic location along the atrioventricular groove. They are typically well circumscribed and are intimate with the coronary arteries and receive a coronary blood supply (Fig. 27.15).

MALIGNANT CARDIAC TUMORS

Primary malignant cardiac tumors comprise fewer than 10% of cardiac tumors in children. The most common is angiosarcoma, which can be associated with hemorrhagic pericardial effusion, cardiac tamponade, and obstruction to cardiac venous inflow channels. Other primary malignant cardiac tumors include fibrosarcomas, lymphosarcomas, giant cell sarcomas, fibromyxosarcoma, sarcomas, rhabdomyosarcomas, undifferentiated sarcomas, leiomyosarcomas, and neurogenic sarcoma. The most common types of secondary (metastatic) cardiac tumors in children include non-Hodgkin lymphoma, leukemia, and neuroblastoma.

FIGURE 27.15. Large pheochromocytoma in the right atrioventricular groove. Left: Subcostal frontal scan. Right: Right coronary artery angiogram demonstrating the vascular tumor (T) adjacent to the proximal coronary artery (RCA). CS, coronary sinus. RA, right atrium; TV, tricuspid valve; RV, right ventricle.

NON-NEOPLASTIC CARDIAC MASSES

As two-dimensional imaging has advanced over the years and with the introduction of transesophageal echocardiography and intracardiac echocardiography, other unusual structures have been identified in the heart that may be mistaken for tumors. Lipomatous hypertrophy of the atrial septum (Fig. 27.16), thrombi, retained foreign bodies, and normal structures such as the transverse sinus may also be mistaken for a cardiac tumor (Fig. 27.17). Appropriate correlation with the history and clinical picture is often helpful in the overall assessment of a cardiac mass.

FIGURE 27.16. Lipomatous hypertrophy of the atrial septum. Transesophageal longitudinal view of the atrial septum demonstrating lipomatous thickening of the superior and inferior limbus (arrows) and the lateral tricuspid annulus. RA, right atrium; LA, left atrium; RV, right ventricle.

FIGURE 27.17. Non-neoplastic cardiac masses. A: Transesophageal echocardiogram at the base of the heart in the short-axis projection demonstrating the transverse sinus (TS) between the great arteries and the left atrial appendage (LAA). Ao, aorta. B: Large thrombus layered along the posterior surface of the left atrium (LA) into the LAA. RA, right atrium; LV, left ventricle. C: Transesophageal four-chamber view demonstrating a retained left atrial infusion catheter. D: Large circular LA thrombus in a patient with mitral valve stenosis. RV, right ventricle.

SUGGESTED READING

Burke A, Jeudy J Jr, Virmani R. Cardiac tumours: an update. Heart. 2008;94:117–123.

Burke A, Virmani R. Pediatric heart tumors. Cardiovasc Pathol. 2008;17:193–198.

Carney JA. Differences between nonfamilial and familial cardiac myxoma. Am J Surg Pathol. 1985;9:53–55.

Cho JM, Danielson GK, Puga FJ, et al. Surgical resection of ventricular cardiac fibromas: early and late results. Ann Thorac Surg. 2003;76:1929–1934.

Dujardin KS, Click RL, Oh JK. The role of intraoperative transesophageal echocardiography in patients undergoing cardiac mass removal. J Am Soc Echocardiogr. 2000;13:1080–1083.

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Questions

1.Which of the following is the most common primary cardiac neoplasm in childhood?

A.Myxoma

B.Papillary fibroelastoma

C.Fibroma

D.Rhabdomyoma

E.Hemangioma

2.Which syndrome – tumor association is correct?

A.Myxoma – Tuberous sclerosis

B.Rhabdomyoma – Carney complex

C.Hemangioma – Down syndrome

D.Fibroma – Gorlin syndrome

E.Fibroelastoma – Marfan syndrome

3.Cardiac myxomas most commonly arise from which location?

A.Left atrium (free wall)

B.Right atrium (free wall)

C.Left atrium (septum)

D.Right atrium (septum)

E.Right ventricle

4.Which gene is implicated in the formation of cardiac rhabdomyomas?

A.TSC2

B.PRKAR1A

C.KRAS

D.p53

E.MLH1

5.A subset of which of the following tumors has shown sensitivity to pharmacotherapy?

A.Myxoma

B.Rhabdomyoma

C.Hemangioma

D.Fibroma

E.Hemangioma

6.What is the most common primary cardiac malignancy in childhood?

A.Myxoma

B.Rhabdomyoma

C.Angioma

D.Liposarcoma

E.Angiosarcoma

7.Which of the following entities does not represent a neoplastic process?

A.Myxoma

B.Rhabdomyoma

C.Thrombus

D.Angiosarcoma

E.Lipoma

8.Which of the following is found most commonly on a cardiac valve?

A.Rhabdomyoma

B.Papillary fibroelastoma

C.Fibroma

D.Myxoma

E.Cystic tumor of the atrioventricular node

9.What percentage of fetuses with a cardiac rhabdomyoma will have an underlying tumor syndrome?

A.20%

B.40%

C.60%

D.80%

E.100%

10.Which of the following usually arises as an intrapericardial lesion?

A.Teratoma

B.Rhabdomyoma

C.Thrombus

D.Cystic tumor of the AV node

E.Fibroma

Answers

1.Answer: D. Rhabdomyomas account for 50-75% of primary childhood cardiac tumors. Papillary fibroelastoma and myxoma are the most common primary cardiac neoplasms of adulthood.

2.Answer: D. Cardiac fibromas may arise in the setting of Gorlin syndrome (nevoid basal cell carcinoma syndrome). This autosomal dominant condition is characterized by cardiac fibromas, multiple basal cell carcinomas, jaw cysts, and skeletal abnormalities.

3.Answer: C. Cardiac myxomas most frequently arise in the left atrium, attached to the septum, in the region of the valve of the fossa ovalis. When a cardiac myxoma arises in a location other than this site, consideration should be given to the possibility of Carney complex (Myxoma syndrome).

4.Answer: A. Mutations in TSC2, the gene encoding for the regulatory protein tuberin, have been implicated in tuberous sclerosis complex as well as the formation of cardiac rhabdomyomas.

5.Answer: B. Pharmacologic inhibition of the mTOR pathway has shown promise in hastening the regression of cardiac rhabdomyomas without surgical intervention.

6.Answer: E. The most common primary cardiac malignancy of childhood is angiosarcoma, which can be associated with hemorrhagic pericardial effusion, cardiac tamponade, and obstruction to cardiac venous inflow channels.

7.Answer: C. Thrombus, as a consequence of a hypercoagulable state and/or regional wall motion abnormalities, occurs as a product of coagulation and does not represent a clonal/neoplastic process.

8.Answer: B. This papillary tumor most commonly arises on the aortic valve, but may occur on any endocardial surface. It has a predilection to occur on damaged endocardium.

9.Answer: D. About half of patients with tuberous sclerosis have cardiac rhabdomyomas, but upwards of 80% of fetuses with rhabdomyomas have tuberous sclerosis.

10.Answer: A. Infants with a teratoma typically present with respiratory distress, pericardial effusion, signs of cardiac compression, cardiac tamponade, and/or nonimmune hydrops fetalis. Echocardiographically, they are usually a single nonhomogeneous, lobular, intrapericardial mass and almost always are associated with pericardial effusion.